tbuckley/cabot-search huggingface dataset:
Abstract 775: Evaluation of Erb-B2 expression from archival tumor tissue in early stage epithelial ovarian carcinoma patient prognosis
Authors: Kavitha Advikolanu Rao, Anthony Magliocco, Andrew Maksymiuk
Journal: Cancer Research (2022)

Abstract In this retrospective study, Erb-B2 expression was assessed in 106 patients using Paraffin-Embedded Tissue (PET) to determine the prognostic value in Epithelial Ovarian Carcinoma (EOC) patients diagnosed at Saskatoon Cancer Center between the years 1983-1995. Relationship between Erb-B2 positivity and patient tumor characteristics was assessed for Overall Survival (OS) and Relapse-Free Survival (RFS) by Kaplan-Meier method. Based on the intensity of stain with a polyclonal antibody (A485, 1/400 dilution), cases with markedly intense cytoplasmic and membranous immunoreactivity were classified as Erb-B2 over-expressors. Erb-B2 was overexpressed in 13 (12%) cases. The mean age of the patients was 56 years (range 18-84 years). The patient population consisted of 64 Stage I and II, Early Stage (ES) and 36 cases with Stage III and IV Advanced Stage (AS). Data on histologic grade was available in 81 cases. 58 patients received platinum-containing regimen, 13 melphalan, and in 9 cases combination chemotherapy. Erb-B2 expression did not influence OS and RFS in these patients. Similarly, there was no significant relation to OS and RFS between Erb-B2 and age, grade, and patients with No Evidence of Disease (NED). Of the 64 cases with ES disease, 16 cases had Grade 2 tumor with Erb-B2 over-expression in 4 cases. Grade 2 tumors with Erb-B2 overexpression indicated significant relationship to OS and RFS, p=0.01, (median = 30 months, CI: 26 - 68) and p=0.05, (median = 15 months, CI: 13 - 68). Furthermore, in 21 cases with ES, Endometrioid histology and Erb-B2 expressors 6/21 (28%) experienced significantly shorter OS compared to non-expressors p=0.005, (median = 48 months, CI: 22 - 74) (mean = 134 months, CI: 124 - 144). In conclusion, Erb-B2 overexpression could be detected in only limited EOC cases in PET and appears to have no prognostic influence. Additionally, endometrioid carcinoma and grade 2, ES certainly reflect the importance of sub-group analysis. In ovarian carcinoma distribution of stage, histology, and grading of tumor cells are conventional markers for prognosis. Finally, Erb-B2 status detected by immunohistochemistry, in a subgroup of patients with high-degree of HER2 positivity/focal amplification may likely have better clinical outcome with anti-HER2 agents. Citation Format: Kavitha Advikolanu Rao, Anthony Magliocco, Andrew Maksymiuk. Evaluation of Erb-B2 expression from archival tumor tissue in early stage epithelial ovarian carcinoma patient prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 775.
Abstract 3707: Moonlighting function of mitochondrial protein VDAC2 provides a potent pharmacological strategy against selective killing of hepatocellular carcinoma
Authors: Piyush Mishra
Journal: Cancer Research (2022)

Abstract Voltage dependent anion channels (VDACs) family of proteins are the most abundant proteins in the outer mitochondrial membrane (OMM). There are three isoforms of VDAC, that are structurally and functionally conserved as far as their ion transport function is concerned. However, there are isoform-specific functions that support distinct pathways. For VDAC2 isoform, an established isoform-specific function is the targeting of the pro-apoptotic Bak protein to the OMM, which stabilizes Bak, leading to its elevated cellular levels. On the surface of OMM, activation and oligomerization of Bak and Bax, another pro-apoptotic protein leads to OMM perforation and release of pro-apoptotic proteins from intermembrane space to the cytoplasm. This is an irreversible step that stimulates the downstream events of apoptotic pathway. Hepatocellular carcinoma (HCC) ranks third in cancer mortality and in the advanced stages is associated with poor prognosis. We observed that unexpectedly, HCC cells are vastly more sensitive to tBid induced apoptosis compared to normal hepatocytes. tBid is a BH3-only pro-apoptotic Bcl-2 family protein, the effect of which is primarily mediated by Bak. We have shown that, in the absence of VDAC2, the Bid-Bak apoptosis pathway is suppressed. VDAC2 protein expression is the lowest in liver and lung among different tissues. We also determined the protein abundances in the HCC lines and normal hepatocytes and found elevated VDAC2 and Bak levels in HCC. Our findings are in line with multiple datasets that show an elevation of VDAC2/Bak expression in human HCC suggesting a potential clinical relevance. We found that combination of an inhibitor of the anti-apoptotic proteins (S63845, a selective Mcl-1 inhibitor), which normally suppresses Bak activation, with an activator of the tBid pathway (TRAIL) enhanced the death of hepatocarcinoma cells with little effect on normal hepatocytes. This treatment strategy was also effective at reducing tumor growth in vivo, but only in tumors expressing VDAC2. Thus, we postulate that increased VDAC2 expression in HCC leads to elevated Bak recruitment to the OMM, which in turn sensitizes HCC to tBid. Therefore, this differential expression provides an excellent opportunity for selective elimination of HCC cells. Citation Format: Piyush Mishra. Moonlighting function of mitochondrial protein VDAC2 provides a potent pharmacological strategy against selective killing of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3707.
Abstract 1554: Functional analysis of human circular RNA_0001587 and its target miRNAs in oral cancer
Authors: Muhammad Jawad Khan, Ghulam Rabia, Abdullahi Dandare, Hassaan Mehboob Awan, Afraz Ahmad Raja
Journal: Cancer Research (2022)

Abstract Oral cancer is the sixth most aggressive malignancy around the world and accounts for 90% of head and neck lesions. It is the most prevalent type of cancer in South Asian countries and contributes to around 25% of all new cancer cases in the region. The involvement of non-coding circular RNAs (circRNAs) in various disease pathology has been reported. However, their role as diagnostic or therapeutic biomarkers is still unclear and needs to be further explored. This study was aimed to identify the role of hsa_circ_0001587 and competing endogenous RNA (ceRNA) mechanism in early diagnosis or as a therapeutic target for oral cancer. For this purpose, lists of circRNAs, miRNAs, and differentially expressed genes (DEGs) involved in oral squamous cell carcinoma (OSCC) were identified from the reported literature. Circinteractome was used to obtain target miRNAs that potentially bind to hsa_circ_0001587. Five miRNAs were selected for further in silico analysis on the basis of maximum target sites. Data were subjected to functional enrichment analysis, pathway analysis, and gene homology studies.Our results showed active participation of both hsa_circ_0001587 and its target miRNAs (miR-548c-3p, miR-520h, miR-1827, miR-607, and miR-579) in oral carcinogenesis via the regulation of genes including AKT, GADD45, PKA, PKC, and CASP8. Dysregulation of these genes disturbed the immune system, signaling pathways, cellular compartment activities, and molecular functions, indicating their role in tumor initiation and progression. Furthermore, it was predicted that hsa_circ_0001587 enhances the expression of genes for the RAS signaling pathway via its sponging effect on miR-548c-3p and miR-607. Noncoding RNAs including hsa_circ_0001587 and target miR-548c-3p and miR-607 play a critical role in the pathogenesis of OSCC. It is therefore suggested that hsa_circ_0001587 and its target miRNAs could be used as potential biomarkers for oral cancer. Citation Format: Muhammad Jawad Khan, Ghulam Rabia, Abdullahi Dandare, Hassaan Mehboob Awan, Afraz Ahmad Raja. Functional analysis of human circular RNA_0001587 and its target miRNAs in oral cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1554.
Abstract 5701: HDAC inhibition decreases YAP1 expression but parodoxically activates TEAD transcription by the AP-1 pathway in breast cancer
Authors: Ting-Yi Lin, Yi-Ru Tseng, Naikuan Wang, Ta-Chung Chao, Chun-Yu Liu, Ling-Ming Tseng, Jiun-I Lai
Journal: Cancer Research (2022)

Abstract The Hippo pathway is an evolutionally conserved pathway that is crucial in numerous aspects of cell biology, including contact inhibition, cell density, and others. Hippo pathway is well reported to be dysregulated in multiple cancer types and plays important oncogenic roles in human cancers. In mammalian cells, YAP is regulated by a phosphorylated cascade mediated by the kinases MST1/2 and LATS1/2, known as the canonical Hippo pathway. These upstream kinases phosphorylate YAP/TAZ and leads to its cytosolic degradation. Perturbation of the Hippo pathway leads to YAP intranuclear translocation and downstream activation of target genes, inducing proliferative signals and thus initiating oncogenesis. Novel mechanism linking the hippo pathway to various oncogenic mechanisms are rapidly discovered and reported, further establishing the significance of this pathway and its role in cancer biology. Breast cancer is the top leading cause of cancer in women and poses a significant morbidity and economic burden on society. Hormone positive (defined as positivity of the estrogen receptor ER and/or the progesterone receptor PR) breast cancer composes 70% of breast cancer. Endocrine therapy, chemotherapy, and more recently, CDK4/6 inhibitors and PI3K inhibitors are currently approved strategies towards breast cancer. Histone deacetylase (HDAC) inhibitors have been FDA approved for several hematological cancers, and recently have shown inconsistent results in clinical trials for breast cancer. In our study, we demonstrate and characterize a link between HDAC inhibition and the Hippo pathway. We discover that HDAC inhibitors suppress YAP expression both transcriptionally and translationally. Paradoxically, we demonstrate that although YAP is downregulated, TEAD mediated transcription of downstream Hippo targets is activated. Mechanistically, HDAC inhibition leads to upregulation of the AP-1 transcriptional machinery that cooperates with TEAD to facilitate transcription. By RNA-seq, chromatin studies and CRISPR knockout studies, we confirm that HDAC inhibition have the ability to activate downstream of Hippo pathway, suggesting a possible mechanism for breast cancer resistance towards HDAC inhibitor. Co-targeting HDAC inhibition and AP-1 results in enhanced efficacy of HDAC inhibitors and may be a promising approach for development towards breast cancer. Citation Format: Ting-Yi Lin, Yi-Ru Tseng, Naikuan Wang, Ta-Chung Chao, Chun-Yu Liu, Ling-Ming Tseng, Jiun-I Lai. HDAC inhibition decreases YAP1 expression but parodoxically activates TEAD transcription by the AP-1 pathway in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5701.
Abstract 5655: Brefeldin A mediates integrated stress response and in combination with Navitoclax induces apoptosis in prostate cancer cells
Authors: Akira Ohtsu, Seiji Arai, Tatsuhiro Sawada, Yoshiyuki Miyazawa, Yoshitaka Sekine, Kazuhiro Suzuki
Journal: Cancer Research (2022)

Abstract Introduction and Objectives: Metastatic castration resistance prostate cancer is a lethal disease. New AR-axis-targeted agent are available, but they will eventually become ineffective. Brefeldin A, an endoplasmic reticulum (ER) protein transport inhibitor, has been shown to cause ER stress. Navitoclax is a BH3 mimetic drug that targets anti-apoptotic proteins (BCL2 and BCLXL) and induces apoptosis in some solid tumors. Here, we investigated the efficacy of Brefeldin A combined with navitoclax on prostate cancer cells. Materials and Methods: We assessed the effect of combination therapy for prostate cancer cells using MTS assay, qRT-PCR, luciferase assay, and western blot. Results: Combination therapy with Brefeldin A and navitoclax synergistically decreased cell viability in prostate cancer cells. Mechanistically, Brefeldin A induced MCL1 degradation and, combined with navitoclax, drove apoptosis. Further, integrated stress response was at least in part involved in Brefeldin A-induced MCL1 degradation. Conclusions: Combination therapy with Brefeldin A and navitoclax shows synergistic anti-tumor effects in prostate cancer cells. These results suggest that Brefeldin A might still be effective in prostate cancer if used with navitoclax. Citation Format: Akira Ohtsu, Seiji Arai, Tatsuhiro Sawada, Yoshiyuki Miyazawa, Yoshitaka Sekine, Kazuhiro Suzuki. Brefeldin A mediates integrated stress response and in combination with Navitoclax induces apoptosis in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5655.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2022)

A New T-cell Player in the Attack on Cancer CD8 þ T cells undergo the process of exhaustion following persistent stimulation, leading to a diverse array of CD8 þ T cells in tumors that express unique combinations of inhibitory receptors.While profiling breast tumors from PyMT mice, Chou and colleagues identified a new type of innate-like T cell with cytotoxic killing potential (ILTCK) that also controlled tumor progression.Using both mouse models of breast cancer as well as human colorectal cancers, they identified ILTCKs as a subset of CD8 þ T cells with low expression of PDCD1 and TOX, both associated with T-cell exhaustion.However, ILTCKs also expressed KLRB1C (NK1.1) and GZMB and were unique in expressing CD8aa dimers and the gamma subunit of the high affinity Fc receptor for IgE (FCER1G).Unlike conventional CD8 þ T cells, the repertoire of T-cell receptors used by ILTCKs remained very diverse, suggestive of broad tumor reactivity.Thymic ILTCKs had a distinct developmental program that continuously produced new cells that could migrate to tumors.Tumor-derived IL15 was critical for survival and function of ILTCKS against cancers.Transfer of ILTCKs more effectively controlled PyMT breast cancer in mice compared with conventional CD8 þ T cells.
Abstract 5911: Soybean products consumption decreases risk for gastric cancer: Results from the Health Examinees study
Authors: Woo-Kyoung Shin, Hwi-Won Lee, Dan Huang, Katherine De la Torre, Sukhong Min, Aesun Shin, Jong-koo Lee, Jung Eun Lee, Daehee Kang
Journal: Cancer Research (2022)

Abstract Background: Twenty percent of soy production is consumed directly by humans worldwide. However, epidemiological findings on the association between soybean products consumption and gastric cancer risk remain inconsistent. We evaluated the relationship between soybean products consumption and the risk of gastric cancer in a prospective cohort study in Korea. Methods: This prospective cohort study included a total of 139,267 participants (men 46,953 and women 92,314) aged 40-69 years from the Health Examinees-Gem (HEXA-G) study between 2004 and 2013. Information on cancer diagnosis was retrieved from the Korea Central Cancer Registry until 31 December 2018. Multivariate hazard ratios (HRs) and 95% of confidence intervals (CIs) for the risk of gastric cancer according to the consumption of soybean products were estimated using Cox proportional hazards models with age as the time scale. Results: A total of 884 incident cases of gastric cancer (men 480 and women 404) occurred over an average follow-up period of 9.20 years (men 9.18 years and women 9.21 years). We found that soybean products consumption is associated with the lower risk of gastric cancer among Koreans (the multivariate HRs for tofu consumption of more than two servings/week were 0.93 (95% CI: 0.68, 1.26; NS) among women and 0.63 (95% CI: 0.45, 0.89) among men). Among men with a body mass index of less than 25kg/m2, increased consumption of soybean paste (p for trend = 0.0188) and tofu (more than two servings/week vs. almost never consumed; HR 0.51 (0.32, 0.82) p for trend = 0.0095) was associated with decreased risk for gastric cancer. Conclusion : Our results suggest that a high consumption of soybean products has a protective effect against gastric cancer Citation Format: Woo-Kyoung Shin, Hwi-Won Lee, Dan Huang, Katherine De la Torre, Sukhong Min, Aesun Shin, Jong-koo Lee, Jung Eun Lee, Daehee Kang. Soybean products consumption decreases risk for gastric cancer: Results from the Health Examinees study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5911.
Abstract 1543: Regulatory role of miR-410 in prostate cancer
Authors: Amritha Sreekumar, Nikhil Patel, Sharanjot Saini
Journal: Cancer Research (2022)

Abstract Prostate cancer (PCa), a leading cause of male cancer related mortality, is dependent upon androgens acting via androgen receptor (AR) signaling. Androgen targeted therapies are often used as the first line of treatment for prostate cancer that are effective initially. However, PCa eventually progresses to castration-resistant stage that has limited treatment options. Castration-resistant prostate cancer (CRPC) is treated by second generation of AR pathway inhibitors such as Enzalutamide and Abiraterone. Resistance to these agents develop owing to various mechanisms such as evolution to androgen-independent neuroendocrine prostate cancer (NEPC). In this study, we examined the potential role of miR-410 in different stages of prostate cancer. Analyses of miR-410 in PCa clinical samples and patient-derived xenograft (PDX) models showed that miR-410 is frequently upregulated in PCa. Its expression was further increased in CRPC cases with neuroendocrine differentiation (NED). We examined the functional role of miR-410 by stably expressing miR-410 in androgen dependent and androgen independent cell lines. Our data suggests a context dependent role of miR-410 in prostate cancer cell lines. In androgen independent cell line, miR-410 plays an oncogenic role by impacting epithelial to mesenchymal transition (EMT) via directly targeting SNAIL. Also, it was found to increase the expression of neuronal genes such as Synaptophysin and neural transcription factor BRN2. However, in androgen dependent cell line, miR-410 was found to target PTEN. In conclusion, our data suggests that miR-410 play an important regulatory role in prostate cancer with effects on EMT and neuronal differentiation programs. Citation Format: Amritha Sreekumar, Nikhil Patel, Sharanjot Saini. Regulatory role of miR-410 in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1543.
Abstract 4052: Evaluation of anti-tumor activity of SB-216, a novel potent tubulin inhibitor, in pancreatic cancer
Authors: Rui Wang, Satyanarayana Pochampally, David Hamilton, Duane D. Miller, Wei Li
Journal: Cancer Research (2022)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with high mortality. It is the 4th leading cause of cancer-related death in the U.S. and has the lowest 5-year survival rate among all cancer types. One of the main hurdles for the treatment is limited effective chemotherapy and rapidly acquired resistance against it. Advanced PDAC research and various treatment options only showed minimal enhancement to the overall survival outcomes. Hence more effective drugs and therapies are in need for improving overall therapeutic outcomes for PDAC patients. Recently, we reported the discovery of a new generation of tubulin inhibitors (SB-216) that targets the colchicine binding site and serves as a potent anti-cancer agent for various cancer types. Here, we evaluated the in vitro effects of SB-216 on the PDAC cell lines in comparison with one of the first-line treatment paclitaxel. We also established luciferase labeled Mia PaCa-2 cell line, Mia PaCa-2-Luc, for live monitoring tumor progression and evaluating the anti-tumor effect in subcutaneous mouse models. The results showed that SB-216 effectively inhibited cell proliferation, colony formation, and cell migration dose-dependently at low nanomolar concentrations. Immunoblotting also confirmed SB-216 induced cell apoptosis in a dose-dependent manner. Cell cycle arrest assay confirmed that SB-216 can arrest cells in the G2/M phase. In vivo study suggested that SB-216 inhibited tumor growth significantly in Mia PaCa-2-Luc subcutaneous xenograft model with low toxicity. Our preclinical data demonstrated the potential of SB-216 to inhibit proliferation and induce apoptosis in PDAC cells, indicating a promising chemotherapy agent in treating PDAC. However, further evaluations are warranted in orthotopic and PDX tumor models for clinical significance. Citation Format: Rui Wang, Satyanarayana Pochampally, David Hamilton, Duane D. Miller, Wei Li. Evaluation of anti-tumor activity of SB-216, a novel potent tubulin inhibitor, in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4052.